Most hospitalized infants experience painful procedures as a part of their care. Repeated or prolonged exposure to pain during early life is associated with permanent changes in brain structure and function and may lead to behavioral and developmental disabilities. Caregivers recognize the need to treat pain in infants but may be reluctant to administer analgesics because of potential short- and long-term side effects. Assessing pain in this vulnerable patient population is difficult as their responses are nonspecific and vary based on developmental stage. This difficulty may lead to both over- and under-treatment of pain, placing infants at risk for permanent neurologic injury. We propose to develop models and computer algorithms to automatically and continuously assess pain in neonates based on behavioral and physiological pain indicators. To achieve this goal, the proposal has two aims: aim 1- Continuously and synchronously record contextual, behavioral and physiological signals from neonates in the NICU while they are undergoing prolonged acute pain; aim 2 - developing a multimodal system for assessing postoperative pain in neonates. The proposed system would generate continuous and standardized pain scores comparable to those obtained by conventional nurse-derived pain scores. It would improve care outcomes by enhancing the assessment of pain while decreasing the burden of pain documentation. It can also eliminate issues of inter-rater reliability associated with conventional neonatal pain assessment. The proposed data collection plan was designed based on our preliminary results and statistical analysis. The proposed system will be evaluated using standard performance metrics, such as accuracy, precision, recall, Cohen?s kappa coefficient, or their variations. The interdisciplinary team includes a neonatologist, Dr. Ho, who is a faculty of both USF College of Medicine and College of Nursing. She practices and oversees the clinical research projects at the Tampa General Hospital NICU (the teaching hospital for USF Health). She ensures the team?s access to the NICU patient population for enrollment. She supervises the performance of the study including nursing pain assessment, video recording, and data collection. The team also includes a professor in nursing who specializes in neonatal opioids dependence and pain, an experienced research nurse, two computer science professors, and one statistics professor. The proposed work aligns very well with the NINR?s mission ?to promote and improve the health of individuals, families, and communities.? The proposed neonatal pain assessment approach will provide a tool for nurses to assess pain continuously and more accurately. Pain is one of the critical factors affecting the brain development in neonates, especially in preterm neonates, with chronic illnesses. The incidence of perterm neonates exposed to pain in high and pain assessment and management remain a primary focus of neonatal nursing research. For infants in the NICU coping with pain, the proposed nursing research will enable proper pain treatment that will also improve their long-term outcomes and development.